
1. Field of the Invention
The present invention relates to a novel aging-suppressing polypeptide in animals, DNA encoding the polypeptide, an antibody recognizing the polypeptide, a ligand for the polypeptide of the present invention, a compound inhibiting a specific binding between the polypeptide and ligand of the present invention, and a compound enhancing the expression of an aging-suppressing gene encoding the aging-suppressing polypeptide of the present invention.
2. Brief Description of the Background Art
The aging phenomenon refers to deterioration of individuals, in terms of change in their functions and appearances, which is generally promoted by the advance in aging. It is known that the frequency of the onset of various adult diseases increases with aging. Therefore, pharmaceutical agents capable of controlling aging in a certain form are expected to be developed as therapeutic agents or preventive agents of adult diseases and as protective agents or preventive agents against functional and apparent deterioration. However, no pharmaceutical agents having these scientifically verified effects have been reported.
Throughout the world, research directed to aging in individuals at the genetic. level has just started, and no molecular genetics information relating to aging in individuals has been presented so far. However, several types of genetic premature aging syndromes are known, including Werner""s syndrome, Hutchinson-Gilford syndrome (progeria), Down""s syndrome, Turner""s syndrome, Louis Barr""s syndrome, Rothmond Thomson syndrome and the like (Daizabuzo Fujimoto, eds., Mechanism and Control of Aging, IPC, 1993).
The causative gene of Werner""s syndrome has been identified as the gene encoding helicase [Science, 272: 258 (1996)]. Various mutations have been observed in the genes from the patients with Werner""s syndrome. It is believed that no normal helicase protein is produced in the patients due to the mutation of the gene and, therefore, its function is not expressed so that a syndrome resembling premature aging may develop.
Based on the above, a suggestion has been presented that a gene relating to aging is present and that aging is promoted through the mutation of the gene. Because other causative genes are also present for other types of genetic premature aging syndromes, it is believed that a plurality of genes may be involved in aging.
If an aging syndrome occurs as a result of loss in function of a gene involved in aging, therapeutic treatment would be useful, such treatment comprising supplementing the function of the gene, i.e. administering a protein product encoded by the gene or expressing the protein product in genetic treatment fashion. Also, if aging can be controlled, except for a genetic premature aging syndrome, various adult diseases occurring in close relation to aging would be treated or prevented.
The gene of the present invention is different from the causative gene of Werner""s syndrome.
No measure is known for treating, preventing or diagnosing adult diseases of which the frequency of the occurrence increases based on aging; for protecting, preventing or diagnosing functional and apparent deterioration based on aging; or for treating and diagnosing a premature aging syndrome. The present invention is useful for such a measure.
The present invention relates to a polypeptide having an activity of suppressing aging in animals including humans; a therapeutic agent for a syndrome resembling premature aging, a therapeutic agent for adult diseases or an aging-suppressing agent, each comprising the polypeptide; DNA encoding the polypeptide; a therapeutic agent for a syndrome resembling premature aging, a therapeutic agent for adult diseases or an aging-suppressing agent, each comprising the DNA; a method for improving livestock using the DNA; a recombinant DNA prepared by inserting the DNA into a vector; a transformant harboring the recombinant; a method for producing the polypeptide of the present invention using the transformant; an antibody recognizing the polypeptide; a method for detecting the polypeptide of the present invention or a method for diagnosing aging, each using the antibody; a method for screening a ligand for the polypeptide of the present invention; the ligand; a method for screening a compound inhibiting a specific binding between the polypeptide and ligand of the present invention; and a compound prepared by the screening method.
The symbols used in the drawings are described below.
bp: base pairs
kb: kilobase pairs
IFN-xcex3: interferon-xcex3 gene
Amp, Ap or Apr: ampicillin resistant gene derived from pBR322
rop+: rop gene
PletI: letI promoter
Ptrp: trp promoter
PSE: simian virus 40 (SV40) early gene promoter
PMO: long terminal repeat (LTR) promoter of Molony mouse leukemia virus
Hyg: hygromycin resistant gene
G418r: G418 resistant gene
dhfr: dihydrofolic acid reductase gene
P1: P1 promoter derived from pBR322
Ptk: promoter of herpes simplex virus (HSV) thymidine kinase (tk) gene
Sp.xcex2G: rabbit xcex2-globin gene splicing signal
A.xcex2G: rabbit xcex2-globin gene poly(A) addition signal
A.SE: simian virus 40 (SV40) early gene poly(A) addition signal
Atk: poly(A) addition signal of herpes simplex virus (HSV) thymidine kinase (tk) gene